It has been appreciated for over 30 years that visual experience during an early postnatal critical period of development produces permanent modifications of the connectivity, physiology and function of the visual cortex. Besides the obvious relevance of this neural plasticity to the development of visual capabilities in humans and animals, it seems likely that similar processes form the basis for some forms of learning and memory in the adult brain. Significantly, like learning, visual cortical plasticity requires the activity of neuromodulatory systems. Considerable progress has been made in identifying the specific changes in visual cortex that result from rearing the animals in different environments, but the detailed mechanisms that underlie these modifications has remained elusive. Recently, however, advances in understanding the receptor mechanisms that mediate synaptic excitation and inhibition in the visual cortex during development have provided an exciting new opportunity to investigate the mechanisms of experience- dependent brain modification. The long-term goal of this project is to elucidate these mechanisms of experience-dependent cortical plasticity. Slices of visual cortex maintained in vitro will be used to study elementary forms of activity-dependent synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). Changes in LTP and LTD during development correlate with changes in naturally-occurring synaptic modification. Our specific aims are to investigate how the properties of LTP and LTD depend on neuromodulators, how these properties change in different cortical layers during development, and to understand the mechanisms which underlie these changes. The study of how LTP and LTD are regulated could yield insights into the mechanisms that are responsible for the critical period.